1. Field of the Invention
This invention relates to novel prostaglandin intermediates, and more particularly novel prostaglandin E intermediates leading to new PGEs having useful physiological properties.
2. Description of the Prior Art
The prostaglandins comprise one of the most unique and remarkable groups of chemical compounds to emerge in recent years. Extensive research with these agents, conducted largely during the last decade, has provided new insights in the fundamental biological processes and has offered a promise of new potent therapeutic agents.
Chemically, prostaglandins are fatty acids of usually about 20 carbon atoms which contain a 5-membered ring, having 2 attached aliphatic side chains, one carrying a carboxylic acid group at the terminus.
The basic structure, prostanoic acid, is shown as I. ##STR3## Chemical variations, involving hydroxyl, carbonyl, and structural variances such as unsaturated groups form the various prostaglandins. An abbreviation system for naming these agents is widely used. Following the letters of PG (prostaglandin), the designation of A, B, E, and F is used to denote the specific ring structure. For example, prostaglandin E.sub.1 (PGE.sub.1) has the following structure: ##STR4## Prostaglandin E.sub.2 (PGE.sub.2) has the following structure: ##STR5##
For a discussion of the stereochemistry of the prostaglandins, reference is made to Nature, vol. 212, page 38 (1966).
The prostaglandins are synthesized in the body from poly-unsaturated fatty acids by the formation of a 5-membered ring (cyclopentane ring) and incorporation of three oxygen atoms at certain positions. One of the common fatty acid precursors who are natural prostaglandins is arachidonic acid, the precursor of prostaglandin E.sub.2. The main source of arachidonic acid is the phospholipids, which are found in the cell membrane.
The PGE.sub.2 compounds are extremely potent in causing stimulation of smooth muscle, and are also highly active in potentiating other known smooth muscle stimulators, for example, oxytocic agents, e.g., oxytocin, and the various ergot alkaloids including derivatives and analogs thereof. PGE.sub.2 is also useful as an hypotensive agent to reduce blood pressure in mammals, including man. PGE.sub.2 also increases the flow of blood in the mammalian kidney, thereby increasing volume and electrolyte content of the urine. Therefore, the compound is useful in managing cases of renal disfunction, especially those involving blockage of the renal vascular bed.